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Fetal anomalies

Gene: MSH6

Amber List (moderate evidence)
MSH6 (mutS homolog 6)
EnsemblGeneIds (GRCh38): ENSG00000116062
EnsemblGeneIds (GRCh37): ENSG00000116062
OMIM: 600678, Gene2Phenotype
MSH6 is in 39 panels

5 reviews

Ida Ertmanska (Genomics England Curator)

This gene and phenotype were reviewed during meetings in July and August 2026. The meetings included representatives of the North Thames and Central and South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Louise Carr (North Thames GLH), Sarah Graham & Elizabeth Young (Central & South GLH), and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Sunayna Best, Soo-Mi Park & Tessa Homfray (R21 Clinical Oversight Group).
Created: 29 Oct 2026, 4:13 p.m. | Last Modified: 29 Oct 2026, 4:13 p.m.
Panel Version: 8.26
Created: 29 Oct 2026, 4:13 p.m.
Last Modified: 29 Oct 2026, 4:13 p.m.
Panel version: 8.26

Vicki Harrison (Wessex Clinical Genetics Service)

Green List (high evidence)

Reported biallelic variants in cases with early onset cancers. Can't see reports of structural anomalies. This gene is included as is a MMR gene and therefore will be included as green in the panel.
Created: 29 Oct 2026, 3:51 p.m. | Last Modified: 29 Oct 2026, 3:51 p.m.
Panel Version: 8.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mismatch repair cancer syndrome 3, OMIM:619097

Publications

Created: 29 Oct 2026, 3:51 p.m.
Last Modified: 29 Oct 2026, 3:51 p.m.
Panel version: 8.25

Arina Puzriakova (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2025 & January 2026. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Created: 10 Mar 2026, 11:35 a.m. | Last Modified: 10 Mar 2026, 11:35 a.m.
Panel Version: 6.148
Created: 10 Mar 2026, 11:35 a.m.
Last Modified: 10 Mar 2026, 11:35 a.m.
Panel version: 6.148

Anna de Burca (Oxford University Hospitals NHS Foundation Trust)

I don't know

CMMRD - very rare condition but ACC reported in a statistically significant number of cases therefore likely to be a genuine association. CNS tumours and developmental venous anomalies, particularly in the PF, seem to be associated but these would not typically meet criteria for R21. Theoretically, impaired mismatch repair might predispose to other anomalies. Interestingly, expert guidelines 2021 do NOT mention structural anomalies apart from DVM. MSH6 is the second most common cause of CMMR-D; penetrance in heterozygotes is lower than MLH1/MSH2. Rating Amber, to review again following wider discussion.
Created: 10 Mar 2026, 11:27 a.m. | Last Modified: 10 Mar 2026, 11:27 a.m.
Panel Version: 6.147

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mismatch repair cancer syndrome 3, OMIM:619097

Publications

Created: 10 Mar 2026, 11:27 a.m.
Last Modified: 10 Mar 2026, 11:27 a.m.
Panel version: 6.147

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Rate all Lynch syndrome genes as Red.
Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.
Panel Version: 0.311
Comment on mode of inheritance: The Mode of inheritance in the Additional PAGE list was recorded as 'Monoallelic' with a Confirmed rating. Phenotype was changed to Biallelic following clinical review.
Created: 24 Mar 2019, 5:35 p.m.
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as Green. Additional notes from clinical review: Include with biallelic inheritance only- phenotype presents in childhood, but these rare tumours could potentially present neonatally. Action taken: Changed Mode of inheritance from 'monoallelic' to 'biallelic'.
Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed.
Created: 11 Dec 2018, 9:05 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.311

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Amber
  • PAGE Additional Gene List
Phenotypes
  • Mismatch repair cancer syndrome 3, OMIM:619097
Tags
Q3_26_promote_green
OMIM
600678
Clinvar variants
Variants in MSH6
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Nov 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: MSH6 were changed from Mismatch repair cancer syndrome 3, OMIM:619097; Mismatch repair cancer syndrome 276300 to Mismatch repair cancer syndrome 3, OMIM:619097

2 Nov 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q3_26_promote_green tag was added to gene: MSH6.

29 Oct 2026, Gel status: 2

Added New Source, Set Phenotypes, Set publications

Ida Ertmanska (Genomics England Curator)

Source NHS GMS was added to MSH6. Added phenotypes Mismatch repair cancer syndrome 3, OMIM:619097 for gene: MSH6 Publications for gene: MSH6 were updated from to 28562508; 24737826; 38981890; 32354708; 17993636; 22692065; 30166433; 38912246; 33247381

10 Mar 2026, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Added phenotypes Mismatch repair cancer syndrome 3, OMIM:619097 for gene: MSH6

9 Mar 2026, Gel status: 2

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Amber was added to MSH6. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

25 Jul 2019, Gel status: 1

Added New Source, Status Update

Rebecca Foulger (Genomics England curator)

Source Expert Review Red was added to MSH6. Rating Changed from Green List (high evidence) to Red List (low evidence)

24 Mar 2019, Gel status: 4

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: MSH6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

24 Mar 2019, Gel status: 4

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene MSH6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

8 Nov 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: MSH6 was added gene: MSH6 was added to Fetal anomalies. Sources: Expert Review Green,PAGE Additional Gene List Mode of inheritance for gene: MSH6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MSH6 were set to Mismatch repair cancer syndrome 276300